실험견의 급성 저산소성 폐고혈압증에서 K+ Channel 의 역할

Objectives: Numerous studies about mediators in acute hypoxic process have been done. These studies revealed that endothelium derived relaxing factor(EDRF, known as nitric oxide) contributed greatly to the pathogenesis of hypoxic pulmonary hypertension and endothelium derived hyperpolarizing factor(EDHF) regulated the tone of vascular smooth muscle. EDHE is known to open K+ channel, hyperpolarizes vascular smooth muscle cells, closes voltage-dependent Ca++ channel and finally relaxes vascular smooth muscle. Some studies revealed that acute hypoxic pulmonary hypertension was developed by inhibition of EDRF &EDHF. To investigate the role of K+ channel in pulmonary hypertension during acute hypoxia, we measured changes of hemodynamic parameters in experimental dogs after adding glibenclamide(K+ channel blocker), methylene blue(S-guanylate cyclase inhibitor), L-NNA(NO synthase inhibitor) and nicorandil(K+ channel opener and S-guanylate cyclase activator). Methods: Six dogs were anesthetized with thiopental sodium and mechanically ventilated with Harvard volume-cycled animal ventilator. Venous and arterial catheters were placed in the limb vein for infusion and femora} artery to measure systemic arterial pressure. Swan-Ganz catheter was inserted via right internal jugular vein for measuring pulmonary arterial pressure, pulmonary capillary wedge pressure asnd cardiac output. We measured the influence of glibenclamide (3mg/kg). methylene blue(lmg/kg), L-NNA (30mg/kg) and nicorandil(300μg/kg) on the changes of hemodynamic parameters during normoxia and hypoxia. Results: The infusion of nicorandil did not affect mean pulmonary arterial pressure during normoxia and significantly inhibited the increase of mean pulmonary arterial pressure during hypoxia. Glibenclamide did not change mean pulmonary arterial pressure during normoxia, but significantly augmented the increase of mean pulmonary arterial pressure during hypoxia. Methylene blue infusion did not affect mean pulmonary arterial pressure during normoxia, but moderately augmented the increase of mean pulmonary arterial pressure during hypoxia. The infusion of L-NNA did not affect mean pulmonary arterial pressure during normoxia and augmented the increase of mean pulmonary arterial pressure singnificantly during hypoxia, The increase of pulmonary arterial pressure induced by glibenclamide, methylene blue, and L-NNA, under hypoxic state was inhibited by nicorandil. Conclusion: Glibenclamide (K channel blocker) did